The histology of immunologically mediated tumor regression was studied in the syngenic strain 2 guinea pig/line 10 hepatocellular carcinoma tumor system. Tumor regression was induced non-specifically by the intralesional injection of living Bacillus Calmette-Guérin (BCG) in 7-day-old established tumors (diameter 8-10 mm). In untreated line 10 tumors at day 7 a mild to moderate inflammatory reaction was present, which consisted mainly of small mononuclear cells; in addition large mononuclear cells and basophils were present. Intratumoral BCG-treatment induced a prominent increase in the inflammatory reaction due to an influx of small and large mononuclear cells and neutrophils. Small mononuclear cells were identified mainly as lymphocytes whereas large mononuclear cells belonged mainly to the macrophage line. Intratumoral administration of BCG resulted in a granulomatous reaction. A time-related decrease in the number of tumor cells and an increase in inflammation, associated with purulent lysis of the granulomatous tissue, was observed. Specific immune-mediated tumor rejection occurred in animals both after active immunization and after adoptive transfer of immune spleen cells. In actively immunized animals the tumor cells were rapidly rejected and from day 4 onwards no tumor cells could be detected at the injection site. Lymphocytes were the major component of the inflammatory reaction; large mononuclear cells were present to a lesser extent and basophilic granulocytes were regularly observed. After adoptive transfer of immunity with immune spleen cells given simultaneously with an intradermal innoculation of tumor cells, an essentially similar rejection reaction was found, although tumor cell rejection was delayed. Lymphocytes and large mononuclear cells were found in equal proportions, whereas basophilic granulocytes were always present in smaller numbers. After BCG-induced regression and in adoptively transferred immune rejection, a fibroblast component was more prominent than in untreated control tumors. This reaction tended to isolate smaller tumor cell areas into islets of decreasing sizes. In contrast with the fibroblast component of growing tumors, the proliferative pre-existing fibrous tissue in tumors undergoing regression or rejection showed a loosely arranged architecture and contained a marked cellular infiltrate. From the results of the present study it was concluded that the morphological expression of line 10 tumor rejection varies. Without immune cells, BCG is needed for the induction of a local inflammatory reaction, which was granulomatous in type and eventually led to complete tumor cell eradication.(ABSTRACT TRUNCATED AT 400 WORDS)